The Editors of this VolumeProf. Dr. Antonio TogniDepartment of ChemistrySwiss Federal Institute of TechnologyETH-HönggerbergCH-8093 ZürichSwitzerland

This book was carefully produced. Nevertheless, authors, editors and publisher do notwarrant the information contained thereinto be free of errors. Readers are advisedto keep in mind that statements, data,illustrations, procedural details or other itemsmay inadvertently be inaccurate.First Edition 2001

PrefaceFinding molecules which are able to catalyze the reaction between others is an important contribution of molecular chemists to increase the efficiency of chemical reactions whereby our daily life based on consumption of chemicals is shifted closerto an ecologically and economically tolerable equilibrium with our environment.Processes, where large amounts of energy are consumed - mostly in order to overcome the activation barrier of a reaction – will disturb significantly and irreversiblyour living conditions. Considering the fact that only a small part of the world population lives under acceptable conditions, it would be cynical to call for a reduction ofindustrial production and development. On the contrary, the production of finechemicals for any pharmaceutical and agricultural use must increase immensely.Meanwhile, synthetic organic chemistry has reached a level where probably forany molecule composed of the elements carbon, hydrogen, nitrogen, and oxygen (toname only the most relevant elements of functionalized organic molecules) a suitable synthesis can be found via a retro-synthetic approach using the fund of knownreaction principles [1]. However, depending on the complexity of the target molecule (which will increase with our understanding of the interaction of molecular entities with its surroundings) these syntheses correspond actually to reactionschemes including a multitude of single reaction steps. The thermodynamic parameters for any of these steps are given. Also the costs of a reaction calculated peratom (i.e. carbon, hydrogen, nitrogen, oxygen, etc.) are almost fixed by the prices ofthe basic chemicals on the world-market. Making a reaction sequence shorter andinevitable reaction steps faster can reach the aim of increasing the productivitywhile keeping energy consumption on a tolerable level. For example, the – especially stereospecific – synthesis of alcohols or amines requires often a lengthy multistep synthesis by which suitable functionalized intermediates are formed. Clearly,the direct stereospecific addition of water or an amine to a prochiral C=C functionwould be the ultimate response to this problem. However, this addition is connected with a very high activation barrier and without a catalyst (which in its most elegant form may also intervene to control the stereochemistry of the addition process)this reaction is ineffective and useless.This book is divided in eight chapters and each of them is devoted to the state-ofthe art of the homogeneously catalysed addition of E-H or E-E’ heteroelementbonds* to unsaturated substrates with C=C, C≡C and C=X functions (X = O, S). Em* By this term we understand bonds betweenheteroelements in the sense of classicalorganic chemistry, i.e. bonds which do notinclude the element carbon.

IX

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Preface

phasis is not only given to highlight achievements, which have been made in eachdomain, but also to clearly show the limitations. Reactions including the addition ofdihydrogen (hydrogenations) or C-H bonds (C-H activation) are not considered andthe reader is referred to recent monographs covering these topics [2,3]. The orderingof the chapters follows simply the ordering by which the heteroelement is positioned in the periodic table. The addition of reagents containing main group elements is treated first and the one of transition metal containing reagents last. Hencethe first chapter discusses the catalyzed addition of boron reagents and the last onegives an overview about hydrozirconation reactions.A catalyzed hydroboration reaction has first been described in 1985. In the beginning, the advantage of this reaction was seen in the use of cheap boron reagentswhich are easy to handle but little reactive in the non-catalyzed reaction. The considerable progress, concerning the development of the boron reagents and the catalysts employed in these types of reactions, is traced by N. Miyaura in the first chapter. Nowadays a wide variety of catalyst types based on complexes of Ti, Zr, Sm, Ru,Rh, Ir, Ni, Pd, and different boranes are employed which allow to control the stereoselectivity and specificity of the borane addition to a manyfold of substrates containing C=C, C≡C, and C=X multiple bonds. More recently the addition of B-B, B-Si,B-Ge, and B-Sn bonds to unsaturated substrates attracted attention. These reactionsare generally catalyzed by Pd(0) Pt(0) or Rh(I) complexes. They allow the elegantsyntheses of highly functionalized products in few steps. Furthermore, the catalyzedcross-coupling reaction of diboranes, R2B-BR2, with organic halides opened astraightforward route to aryl and allyl boranes which themselves are valuable intermediates.In the second chapter, homogeneously catalyzed hydroalumination reactions ofalkenes and alkynes are surveyed. Although alanes are more reactive than boranesand many hydroaluminations proceed indeed without a catalyst (especially those ofalkynes), metallocene chlorides, such as Cp2TiCl2 or Cp2ZrCl2, nickel or cobalt salts,or palladium(II) complexes not only accelerate the reaction but also influence thestereochemistry of the addition reaction. Apart from (enantioselective) hydroaluminations of carbon-carbon multiple bonds and allyl ether cleavages, the reader willlearn about highly selective reductive ring opening reactions, which were inventedin the group of M. Lautens who is, with M. Dahlmann, the author of this chapter.This reaction is another good example for the short and elegant synthesis of complex molecules by a novel approach using a catalytic heterofunctionalization as thekey step.The transition metal-catalyzed hydrosilylation belongs to the „old-timers“ of catalytic heterofunctionalizations and numerous applications have been established.Therefore, J. Tang and T. Hayashi concentrate in the third chapter on the progressmade in enantioselective hydrosilylations. Frequently, precursor complexes withplatinum and rhodium as active centres and a chiral phosphine as ligand are employed in these reactions. However, recently also palladium complexes carrying amonodendate axial-chiral phosphine were introduced as highly efficient catalystsfor enantioselective hydrosilylations. Furthermore, new lanthanide and group 3metallocene complexes were found to be active complementing the established list

Preface

of d0 metal hydrosilylation catalysts, i.e. titanocenes and zirconocenes. Notableprogress has also been made in the asymmetric syntheses of functionalzsed carbocycles by hydrosilylation of suitable dienes. Catalyzed by chiral palladium(II) oxazoline or rhodium(I) bisphosphine complexes, C-C, C-Si and C-H bonds are stereoselectively formed within one catalytic cycle making the efficiency of catalytic heterofunctionalizations evident.The fourth chapter gives a comprehensive review about catalyzed hydroaminations of carbon carbon multiple bond systems from the beginning of this century tothe state-of-the-art today. As was mentioned above, the direct - and whenever possible stereoselective - addition of amines to unsaturated hydrocarbons is one of theshortest routes to produce (chiral) amines. Provided that a catalyst of sufficient activity and stability can be found, this heterofunctionalization reaction could competewith classical substitution chemistry and is of high industrial interest. As the authors J. J. Brunet and D. Neibecker show in their contribution, almost any transitionmetal salt has been subjected to this reaction and numerous reaction conditionswere tested. However, although considerable progress has been made and enantioselectivites of 95% could be reached, all catalytic systems known to date suffer fromlow activity (TOF < 500 h-1) or/and low stability. The most effective systems are represented by some iridium phosphine or cyclopentadienyl samarium complexes.The discussion of the activation of bonds containing a group 15 element is continued in chapter five. D.K. Wicht and D.S. Glueck discuss the addition of phosphines, R2P-H, phosphites, (RO)2P(=O)H, and phosphine oxides R2P(=O)H to unsaturated substrates. Although the addition of P-H bonds can be sometimesachieved directly, the transition metal-catalyzed reaction is usually faster and mayproceed with a different stereochemistry. As in hydrosilylations, palladium and platinum complexes are frequently employed as catalyst precursors for P-H additions tounsaturated hydrocarbons, but (chiral) lanthanide complexes were used with greatsuccess for the (enantioselective) addition to heteropolar double bond systems, suchas aldehydes and imines whereby pharmaceutically valuable α-hydroxy or α-aminophosphonates were obtained efficiently.In the sixth chapter the activation of O-H bonds of water, alcohols and carboxylicacids, and their addition to multiple bonds is reported. Since the formally oxidativeaddition of ROH gives rise to hydrido(hydroxo) complexes, [MH(OR)Ln] which arepostulated as intermediates in many important reactions (water gas shift reaction,Wacker-chemistry, catalytic transfer hydrogenations etc.) the authors of this chapter,K. Tani and Y. Kataoka, begin their discussion with an overview about the synthesisand isolation of such species. Many of them contain Ru, Os, Rh, Ir, Pd, or Pt andcomplexes with these metals appear also to be the most active catalysts. Their stoichiometric reactions, as well as the progress made in catalytic hydrations, hydroalcoxylations, and hydrocarboxylations of triple bond systems, i.e. nitriles andalkynes, is reviewed. However, as in catalytic hydroaminations the „holy grail“, theaddition of O-H bonds across non-activated C=C double bonds under mild conditions has not been achieved yet.H. Kuniyasu continues the discussion of the activation of group 16 element bondswith an overview on S(Se)-X additions to unsaturated substrates. For some time, it

XI

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Preface

was believed that sulfur compounds „poison“ systematically transition metal complexes by forming very robust metal sulfides. However, as it is shown in this seventhchapter, a wide variety of thiols, disulfides, diselenides, silyl and germyl sulfides andselenides, and thioboranes can be successfully added to carbon carbon muItiplebonds, especially alkynes, with the aid of metal catalysts. Frequently, the „ubiquitous“ metal complexes used in homogeneous catalysis like the phosphine complexes of palladium, platinum, and rhodium can be used to afford a wide range ofchalcogenato compounds. Also cobalt, nickel, and ruthenium complexes, and someLewis-acids were studied as catalysts.A chapter written by A. Igau reviewing hydrozirconations concludes this book. Aswas demonstrated in recent years, the addition of the Schwartz reagent,[Cp2ZrHCl]n, to unsaturated substrates containing C=C, C≡C, C=N, C=P, and C=Oentities allowed the synthesis of a wide range of highly functionalized zirconiumderivatives which proved to be valuable intermediates in organic synthesis. Sincethe primary products of the hydrozirconation reaction contain a highly polar zirconium(δ+) X(δ-) bond (X = C, N, O, etc), they can be easily transformed further bysubstitution reactions with halides or insertion reactions of another equivalent of anunsaturated substrate into the Zr-X bond. Although catalytic hydrozirconations arejust being discovered and most of the reactions described in this chapter are stoichiometric, the reader will find many useful applications of this type of heterofunctionalization.For some of the reactions described in this book, rather precise and detailed ideasabout the reaction mechanism exist. However, for many catalytic reactions, themechanistic understanding is very poor and further experimental studies are certainly needed. Calculations proved to be a highly valuable tool to gain a more precisepicture of the reaction pathways. However, mostly only model systems can be studied due to the complexity of the problem. Anyway, it is the firm believe of the authors that for any reaction with an activation barrier a suitable catalyst can be found.This book shall give an insight into what has been achieved in this area concerningthe synthesis of heterofunctionalized organic molecules. It is the hope of all contributors that future retro-synthetic schemes will include the catalytic approachesoutlined in this book.

In this work, particular attention will be given to the synthesis of organoboron compounds via the metal-catalyzed addition and coupling reactions of H–B, B–B, B–Si,and B–Sn reagents [1, 2]. The classical methods for the synthesis of organoboroncompounds are based on the reaction of trialkyl borates with Grignard or lithiumreagents (transmetalation) or the addition of H–B reagents to alkenes or alkynes(uncatalyzed hydroboration) [3]. Although these methods are now most commonand convenient for large-scale preparations, the metal-catalyzed reactions are advantageous in terms of efficiency and selectivity of the transformations. Hydroborationof alkenes and alkynes is one of the most studied of reactions in the synthesis oforganoboron compounds and their application to organic synthesis. However, catalyzed hydroboration did not attract much attention until Männig and Nöth in 1985[4] reported that a Wilkinson complex [RhCl(PPh3)3] catalyzes the addition of catecholborane to alkenes or alkynes. Although the transition metal complexes significantly accelerate the slow reaction of (dialkoxy)boranes, the catalyzed hydroborationis a more interesting strategy to realize the different chemo-, regio-, diastereo-, andenantioselectivities, relative to the uncatalyzed reaction, because the catalyzed reaction can change the metal-hydride species which interacts with the unsaturated C–Cbond. The addition of diboron tetrahalides B2X4 (X=F, Cl, Br) to unsaturated hydrocarbons (diboration), first discovered by Schlesinger in 1954 [5, 6], is an attractiveand straightforward method to introduce boryl groups into organic molecules, butthe synthetic use has been severely limited because of the instability and limitedavailability of the reagents. Although tetra(alkoxo)diboron dramatically enhancesthe stability of the B–B species at the expense of reactivity for organic nucleophiles,the B–B compounds oxidatively add to low-valent transition metals with the B–Bbond cleavage, thus allowing the catalyzed transfer of boron to unsaturated organicsubstrates. The metal-catalyzed addition of B–B, B–Si, or B–Sn reagents to alkenesor alkynes provides a new class of boron compounds including heterofunctionalizedalkyl-, alkenyl-, and allylboronates. The cross-coupling reaction of metal-boryl

1

2

1 Hydroboration, Diboration, Silylboration and Stannylboration

reagents is an alternative to the transmetalation method and perhaps a more convenient and direct protocol for the synthesis of organoboron compounds from organic halides and other electrophiles.Much attention has recently been focused on organoboronic acids and their estersbecause of their practical usefulness for synthetic organic reactions including asymmetric synthesis, combinatorial synthesis, and polymer synthesis [1, 3, 7–9], molecular recognition such as host-guest compounds [10], and neutron capture therapy intreatment of malignant melanoma and brain tumor [11]. New synthetic proceduresreviewed in this article will serve to find further applications of organoboron compounds.

1.2

Metal-Catalyzed Hydroboration1.2.1

Hydroboration of Alkenes and Alkynes

Most studies of catalyzed hydroboration have employed catecholborane 1 (HBcat)[12] because of its high reactivity for various transition metal catalysts (Scheme 1-1).However, pinacolborane 2 (HBpin) [13] has recently been found to be an excellentalternative because it is a more stable, easily stored and prepared hydroborationreagent. The high stability of the resulting products (pinacol esters of alkyl- or 1alkenylboronates) to moisture and chromatography is also very convenient for organic chemists. Other borane reagents including 4,4,6-trimethyl-1,3,2-dioxaborinane (3) [14], oxazaborolidines (4) [15] , benzo-1,3,2-diazaborolane (5) [16], and borazine (8) [17] may also be used, but the scope of these reagents remains to be explored.There is no systematic study of the effect of borane reagents, and the best choicewould be highly dependent on the catalysts and substrates. A series of di(alkoxy)boranes have recently been synthesized and subjected to hydroboration of cyclopentene at ambient temperature in the presence of RhCl(PPh3)3 (Scheme 1-2) [18]. TheO

O

O

H B

H B

H BO

1 (HBcat)

N

Me

O

Ph

H B

H B

O

O

2 (HBpin)

3

Cl

O

H

O

H

H B

H BCl

OCl6

Scheme 1-1

NH

4

ClO

HN

7

Borane Reagents for Catalyzed Hydroboration

NB

5HBNH8

NB

HH

1.2 Metal-Catalyzed HydroborationRhCl(PPh3)3 (< 1 mol%)+

HB(OR)2(2 equivs)

B(OR)2

CDCl3/r.t.borane

time for >90% conversion

7

4 min

6

30 min

1

90 min

HB(OCH2Ph)2

no reaction

Effect of Borane Reagents

Scheme 1-2

superiority of more Lewis-acidic boranes is suggested because acyclic dialkoxyboranes do not participate in the catalytic cycle and tetrachlorocatecholborane (6) reacts adequately faster than catecholborane. However, the less acidic six-memberedborane 7 is, unexpectedly, the best reagent for the rhodium-catalyzed hydroboration.Hydroboration of styrene derivatives has been extensively studied, and perhapsthese are the best substrates to consider in a discussion of the efficiency and selectivity of the catalysts (Table 1-1). A neutral rhodium-phosphine complex

RhCl(PPh3)3 is the most studied catalyst for hydroboration of alkenes, but the complex is unfortunately highly sensitive to air. Thus, handling the catalyst under argonor air results in different regioselectivity (entries 1 and 2) [19, 20]. The changes inregioselectivity resulted from lowering the triphenylphosphine-to-rhodium ratio viaoxidation of phosphine to the oxide (Scheme 1-3) [21]. Thus, the in situ preparationof the catalyst from [RhCl(cod)]2 and a limited amount of phosphine (entries 3–7)[19–23] or the use of an air stable π-allylrhodium complex (entry 8) [24] is a convenient alternative, but the use of a large excess of the ligand should be avoided becauseof its higher coordination ability to the metal than that of alkenes. An addition ofphosphine to [Rh(cod)2]BF4 generates a highly active species to catalyze hydroboration even at temperatures lower than 0°C (entries 9 and 10) [22, 25]. The regiochemical preference giving terminal (10) or internal products (9) depending on the ligandand the valence state of the metal has not yet been well understood. The high internal selectivity of vinylarenes is accounted by a contribution of a π-benzylrhodiumspecies [22]; however, the catalyzed reaction commonly exhibits high internal selectivity for alkenes having an electron-withdrawing group such as vinylarenes, fluoroalkenes [26], and α,β-unsaturated esters or amides [27], and the cationic rhodiumcatalysts would further increase the internal selectivity. The iridium(I) [28] andruthenium(II) or (III) [29] complexes analogously catalyze hydroboration with catecholborane (entries 11–14). Although the neutral phosphine complexes reveal ahigh terminal selectivity, the scope of these catalysts has not yet been studied in detail. The cyclopentadienyl complexes such as Cp2TiMe2 [30] and Cp*2Sm(THF) [31]are excellent catalysts for the addition of boron to the terminal carbon (entries 15and 16). Such high terminal selectivity can be accounted for by steric hindrance ofthe cyclopentadienyl ligand, since the Cp* complex exhibits higher terminal selectivity than that of the Cp ligand and SmI3 [32] results in a mixture of both isomers.The steric effect of borane reagents also plays an important role in selectivity. Pinacolborane selectively adds to the terminal carbon because of its bulkiness (entries17–20), which is in sharp contrast to the internal addition of catecholborane according to the electronic effect of the phenyl group. Although RhCl(PPh3)3 results in acomplex mixture for styrene including regioisomers (9, 10) and a dehydrogenativecoupling product PhCH=CHBpin (entry 17), other Rh(I), Ni(II), and Ir(I) catalystsreveal high terminal selectivity (entries 18–20) [33–34].Various metal complexes catalyze the addition of catecholborane and pinacolborane to aliphatic terminal alkenes (Table 1-2). Neither the borane reagents nor thecatalysts alter the high terminal selectivity, but a titanium catalyst does (entry 3). Although Cp2TiMe2 [30] exhibits high terminal selectivity for vinylarenes, aliphaticalkenes afford appreciable amounts of internal products, whereas an analogousCp*2Sm(THF) [31] allows selective addition of catecholborane to the terminal car-

bon (entry 4), which is due to differences in the metal hydride species participatingin the insertion of alkene (see Section 1.2.2). SmI3 exhibits a unique regioselectivitydepending on the reaction time (entries 5 and 6) [32]. The reaction initially yields amixture of internal and terminal product, but the catalyst slowly isomerizes secondary alkylboronate to the primary one on prolongation of reaction time, thus suggesting reversible formation of the C–B bond. On the other hand, the catalysts do not alter the high terminal selectivity of pinacolborane (entries 7–12) [33, 34, 36].The differences in the steric effect between catecholborane and pinacolborane,and the valence effect between a cationic or neutral rhodium complex reverse the regioselectivity for fluoroalkenes (Scheme 1-4) [26]. The reaction affords one of twopossible isomers with excellent regioselectivity by selecting borane and the catalystappropriately, whereas the uncatalyzed reaction of 9-BBN or Sia2BH failed to yieldthe hydroboration products because of the low nucleophilicity of fluoroalkenes. Theregiochemical preference is consistent with the selectivity that is observed in the hydroboration of styrene. Thus, the internal products are selectively obtained when using a cationic rhodium and small catecholborane while bulky pinacolborane yieldsterminal products in the presence of a neutral rhodium catalyst.The isomerization of internal alkenes to terminal ones before hydrometalation orthe isomerization during hydrometalation results in the formation of terminal prodCH3RF

ucts for internal alkenes. For example, the hydroboration-oxidation of 4-octeneyields terminal or internal alcohols depending on the boranes and catalysts employed (Table 1-3). The cationic rhodium and the iridium complexes are more proneto isomerize the boron atom to the terminal carbon than the neutral rhodium complexes (entries 1 and 2) [20]. A bulky pinacolborane has a strong tendency to isomerize to the terminal carbon [33, 36]. Thus, all selectivities shown in Table 1-3 illustrate the superiority of pinacolborane for the synthesis of terminal boron compounds. The bulkiness of the pinacolato group may have the effect of accelerating βhydride elimination and slowing down the C–B bond formation fromR-Rh(III)-Bpin intermediate so that the rhodium can migrate to the terminal carbonvia an addition-elimination sequence of the H-Rh(III)-Bpin species. An uncatalyzedsequence of hydroboration/isomerization at elevated temperature is an alternativeto synthesizing terminal alcohols from internal alkenes or a mixture of terminal andinternal ones [37].The catalyzed hydroboration of alkynes with catecholborane or pinacolborane affords (E)-1-alkenylboron compounds at room temperature (Table 1-4). TheRhCl(PPh3)3-catalyzed reaction of phenylacetylene yields a complex mixture of tworegioisomers of alkenylboronates (13 and 15), two hydrogenation products of 13 and15, and a trace of a diboration product (entry 1) [19]. The nickel- [33, 39] or palladium-phosphine complexes [40] and Cp2Ti(CO)2 [30] are good catalysts for catecholborane giving selectivity comparable to that of the uncatalyzed reaction (entries 2, 7,8, and 11–13), and Cp2ZrHCl [38], Rh(CO)(PPh3)2Cl [33] or CpNiCl(PPh3) [33] forpinacolborane (entries 4–6 and 9–10). The cis- and anti-Markovnikov addition to terminal alkynes may have no significant advantage over the uncatalyzed reactionsince the same compounds can be reliably synthesized by the uncatalyzed reactionat slightly elevated temperature. However, the differences in the metal hydridespecies between the catalyzed and uncatalyzed reactions often alter the chemo-, regio-, and stereoselectivity. For example, the catalysts reverse the regioselectivity inthe hydroboration of 1-phenyl-1-propyne (entries 7 and 8). The Cp2Ti(CO)2 [30]prefers the addition of boron to the carbon adjacent to phenyl according to its electronic effect, and steric hindrance of the phosphine ligand of NiCl2(dppe) [39] forcesthe addition to the β-carbon. The uncatalyzed hydroboration of thioalkynes with di-

a) 1-Phenylethylborare and 2-phenylethylborate were also produced.b) The reaction was carried out at room temperature in CH2Cl2 inthe presence of Et3N (1 equiv) and excess of alkyne (1.2.equivs).

cyclohexylborane yields 15 because the α-carbon adjacent to the alkylthio group ismore nucleophilic than the β-carbon [41]. However, the nickel- or palladium-phosphine complexes allow a complete reversal of the regiochemical preference, resulting in a selective formation of β-alkylthio-1-alkenylboronates (entries 11 and 12)[39]. The (Z)-1-alkenylboronates have been synthesized by a two-step method basedon the intramolecular SN2-type substitution of 1-halo-1-alkenylboronates with metalhydrides [42] or the cis-hydrogenation of 1-alkynylborates [43]. The rhodium(I)- oriridium(I)-iPr3P complex has recently been found to catalyze the trans-hydroborationof terminal alkynes directly yielding cis-1-alkenylboron compounds (entries 14–15)tBu

H

D

HBcatuncatalyzed

B OO

D

HBcat

tBu-C≡C-D

tBu

[RhCl(cod)]2/4iPr3P/Et3N/CH2Cl2/r.t.

E>99%

B OO

Z>99%

D

D

DtBu

[Rh]

[Rh]

•

tBu

HBcat

tBu

[Rh]Bcat

H16

Scheme 1-5

H

17

Cis- and Trans-Hydroboration of Terminal Alkynes

18

7

8

1 Hydroboration, Diboration, Silylboration and Stannylboration

[44]. The dominant factors reversing the conventional cis-hydroboration to the transhydroboration are the use of alkyne in excess of catecholborane or pinacolboraneand the presence of more than 1 equiv. of Et3N. The β-hydrogen in the cis-productunexpectedly does not derive from the borane reagents because a deuterium label atthe terminal carbon selectively migrates to the β-carbon (Scheme 1-5). A vinylidenecomplex (17) [45] generated by the oxidative addition of the terminal C–H bond tothe catalyst is proposed as a key intermediate of the formal trans-hydroboration.The catalyzed hydroboration of conjugate dienes, 1,2-dienes (allenes), and enynesproceeding though a π-allylmetal intermediate realizes very different regioselectivities relative to the uncatalyzed reactions. The palladium-catalyzed hydroboration ofconjugate 1,3-dienes yields allylboronates via an oxidative addition-insertion-reductive elimination process (Scheme 1-6) [46, 47]. The cis-addition of the H–B bond to adiene coordinated to palladium(0) affords cis-allylboronate (Z>99%), and the selective migration of a hydrogen to the unsubstituted double bond gives a single regioisomer for asymmetric dienes, though analogous reaction of 1,3-pentadiene [46] or1-phenyl-1,3-butadiene [47] fails to yield allylboronates. The rhodium complex givesa complex mixture for alicyclic dienes, but Rh4(CO)12 is recognized to be the bestcatalyst for 1,4-hydroboration of 1,3-cyclohexadiene (92%).R1R1

R2

R2O

HBcat

Me

B

R1

R2

R2

OH

yield/%

R1

R2

H

H

81 (syn>99%)

H

Me

89 (syn>99%)

Me

Me

81

H Pd

PdH

R2

R1Ph

O

Pd(PPh3)4benzene/rt

R1

Me

PhCHO

B

Scheme 1-6

B

Hydroboration of 1,3-Dienes

The uncatalyzed hydroboration of allenes suffers from the formation of a mixtureof monohydroboration and dihydroboration products or a mixture of four possibleregioisomers (19–22) [48]; however, the phosphine ligand on the platinum(0) catalyst controls the regio- and stereoselectivity so as to provide 21 or 22 for alkoxyallenes, and 20 or 22 for aliphatic and aromatic allenes (Scheme 1-7) [49]. The addition to aliphatic and aromatic allenes with Pt(dba)2/2PtBu3 occurs at the internaldouble bond to selectively provide 20, whereas the electronic effect of MeO or TBSOplay a major role in influencing the course of the reaction as evidenced by the preferential formation of the terminal cis-isomer (21) by way of attack from the less-hindered side of the allenes (Z>84–91%). Thus, a platinum(0)/2tBu3P complex affordsthe internal products (20) or the terminal anti-Markovnikov products (21) depending on the electron-donating property of the substituents. On the other hand, a very

1.2 Metal-Catalyzed Hydroboration

R

R1

2

2019

HBpinPt(dba)2/2tBu3Ptoluene/50 °C

O

R1

R1

BO

R2

R1=Bu, R2=H, 79%R1=cyclo-C6H11, R2=H, 91%

R2

O BO

R1

OB O

R1

HBpinR2Pt(dba)2/2tBu3P/toluene/50 °C

21

•

HBpinB OR2Pt(dba)2O/2TTMPP22/toluene/50 °C

R1=tBuMe2SiO, R2=H, 86% (E/Z=9/91)

Scheme 1-7

CH3

R1, R2=-(CH2)5-, 76%

Hydroboration of Terminal Allenes

bulky and basic tris(2,4,6-trimethoxy-phenyl)phosphine (TTMPP) exhibits a characteristic effect which dramatically changes the regioselectivity to the Markovnikov addition (22) for the representative terminal allenes.The hydroboration of enynes yields either of 1,4-addition and 1,2-addition products, the ratio of which dramatically changes with the phosphine ligand as well asthe molar ratio of the ligand to the palladium (Scheme 1-8) [46–51]. (E)-1,3-Dienylboronate (24) is selectively obtained in the presence of a chelating bisphosphinesuch as dppf and dppe. On the other hand, a combination of Pd2(dba)3 withPh2PC6F5 (1–2 equiv. per palladium) yields allenylboronate (23) as the major product. Thus, a double coordination of two C–C unsaturated bonds of enyne to a coordinate unsaturated catalyst affords 1,4-addition product. On the other hand, a monocoordination of an acetylenic triple bond to a rhodium(I)/bisphosphine complexleads to 24. Thus, asymmetric hydroboration of 1-buten-3-yne giving (R)-allenylboronate with 61% ee is carried out by using a chiral monophosphine (S)-(–)-MeOMOP (MeO-MOP=2-diphenylphosphino-2′-methoxy-1,1′-binaphthyl) [52].

The dehydrogenative coupling of borane is a very attractive method since the reaction directly yields (E)-1-alkenylboronates from alkenes (Table 1-5). However, thereaction can be limitedly applied to the synthesis of styrylboron derivatives [15,53–56]. The reported procedures recommend a combination of vinylarene, a sterically hindered borane such as oxazaborolidine 4 or pinacolborane 2, and a phosphine-free rhodium(I) catalyst for achieving selective coupling. The reaction requires more than two equivalents of vinylarene because H2, generated by β-hydrideelimination, hydrogenates a molar amount of vinylarene, as is discussed in themechanistic section. Cp*2Ti exceptionally catalyzes the borylation of ethylene, butthe scope of the reaction for other inactivated alkenes has not yet been explored [55].1.2.2

Catalytic Cycles

Catalyzed hydroboration often results in a complex mixture of products derived notonly from catalyzed hydroboration but also uncatalyzed hydroboration and hydrogenation of alkenes, because the reaction of RhCl(PPh3)3 with catecholborane (HBcat) yields various borane and rhodium species (Scheme 1-9) [19]. The oxidative addition of HBcat to RhCl(PPh3)3 affords a coordinate unsaturated borylrhodiumcomplex (25) [57], which is believed to be an active species of the catalyzed hydroboration. However, further oxidative addition of the borane to 25 generates H2 and adiborylrhodium complex (26) [58]. The diboryl complex 26 will then undergo diboration or reductive monoborylation of alkenes (see Section 1.3.2), and dihydrogenthus generated will hydrogenate a part of the alkenes. Thus, the reaction is oftenaccompanied by small amounts of RCH(Bcat)CH2(Bcat), RC(Bcat)=CH2,RCH=CH(Bcat), and RCH2CH3, along with the desired hydroboration product. Onthe other hand, the degradation of catecholborane makes the reaction more complexwhen the catalyzed reaction is very slow. The phosphine eliminated from the catalyst reacts with catecholborane to yield H3B•L and B2cat3 (cat=O2C6H4) (29) [59]. Although the borane/phosphine complex thus generated fortunately does not hydrob-

1.2 Metal-Catalyzed Hydroboration

+

H3B•L

O B OO

O B OO

O OBO O

29 [B2(cat)3]

30

Rh•L2

3 HBcat

LRhCl•L3 + HBcat

L +

Cl

Catalyzedhydroboration

L

Bcat

25

"BH3"

RhH•L3

H

Rh

slowHBcat

28

LCl Rh

BcatBcat

+ H2

LBH3 + 29

26

RhCl•L3RhH2Cl•L327

Uncatalyzedhydroboration

Diborationsee Section 1.3.2Hydrogenationof alkenes

Scheme 1-9

Reaction of RhCl(PPh3)3 with Cartecholborane (HBcat)

orate alkenes, 29 may contribute to the production of other rhodium species such as30 [24], which has high catalyst activity comparable to that of 25. The reaction oftensuffers from the competitive uncatalyzed hydroboration with BH3, and the formation of such products does not reflect the true selectivity of the catalyzed reactions[19, 60, 61]. The degradation of catecholborane to BH3 and B2cat3 29 is, in general,very slow at room temperature; however, the reaction of BH3 will compete with thecatalyzed hydroboration when the reaction is very slow because of decomposition ofthe catalyst or low catalyst loading or activity. Although there are many probableprocesses leading to side reactions, catecholborane undergoes clean hydroborationwhen the catalyst is selected appropriately.One most important observation for the mechanistic discussion is the oxidativeaddition/insertion/reductive elimination processes of the iridium complex (31)(Scheme 1-10) [62]. The oxidative addition of catecholborane yields an octahedraliridium-boryl complex (32) which allows the anti-Markovnikov insertion of alkyneinto the H–Ir bond giving a 1-alkenyliridium(III) intermediate (34). The electron-